Research proposal: The pathogenesis of ehrlichial and related tick-borne rickettsial pathogens of humans and animals is directly linked to their ability to evade the immune system. Antigenic variation of surface proteins is a major evasion strategy common to all ehrlichial pathogens, often involving very similar antigens. Anaplasma marginale, a bovine pathogen, is closely related to Anaplasma (Ehrlichia) phagocytophila, the causative agent of human granulocytic ehrlichiosis. Investigations of bovine anaplasmosis offer a unique opportunity to study the mechanisms of antigenic variation in a natural animal model under controlled conditions. This project will examine the mechanisms and extent of antigenic variation of MSP3, the major antigen recognized by the hosts immune system, and related antigens. It will also investigate the influences of different environments: the mammalian host, the tick vector and in-vitro cultures, on the expression of the MSP3 antigen in a clonal line of A. marginale. The candidate: The principal investigator is a veterinarian with extensive field experience in parasitic and tick-borne diseases and with a strong desire to become an independent researcher in this field. In preparation for this, the candidate has enrolled in an infectious disease Ph.D. program and has completed courses in statistics, molecular biology, immunology and pathogenesis and has been admitted to candidacy. This proposal will allow his development as an independent researcher and will help elucidating pathogenic mechanisms of vector-borne pathogens in animals and humans. The investigator hopes to apply these findings and the expertise gained toward the development of innovative control strategies. Environment: The training will occur in an interactive environment of clinical and basic scientists. The mentors have extensive experience in the pathogenesis of and immune responses to vector-borne pathogens and have successfully trained previous candidates. The program provides an excellent framework for the proposed training.